Transcriptome analysis reveals a long non-coding RNA signature to improve biochemical recurrence prediction in prostate cancer.

Jinyuan Xu,Shiwei Zhu,Hongyi Zhang,Lili Li,Fulong Yu,Jiali Zhu,Shujun Cheng,Yun Xiao,Jianrong Ran,Xia Li,Yujia Lan

doi:10.18632/oncotarget.25048

Abstract

Despite highly successful treatments for localized prostate cancer (PCa), prognostic biomarkers are needed to improve patient management and prognosis. Accumulating evidence suggests that long noncoding RNAs (lncRNAs) are key regulators with biological and clinical significance. By transcriptome analysis, we identified a set of consistently dysregulated lncRNAs in PCa across different datasets and revealed an eight-lncRNA signature that significantly associated with the biochemical recurrence (BCR)-free survival. Based on the signature, patients could be classified into high- and low-risk groups with significantly different survival (HR = 2.19; 95% CI = 1.67–2.88; P < 0.0001). Validations in the validation cohorts and another independent cohort confirmed its prognostic value for recurrence prediction. Multivariable analysis showed that the signature was independent of common clinicopathological features and stratified analysis further revealed its role in elevating risk stratification of current prognostic models. Additionally, the eight-lncRNA signature was able to improve on the CAPRA-S score for the prediction of BCR as well as to reflect the metastatic potential of PCa. Functional characterization suggested that these lncRNAs which showed PCa-specific expression patterns may involve in critical processes in tumorigenesis. Overall, our results demonstrated potential application of lncRNAs as novel independent biomarkers. The eight-lncRNA signature may have clinical potential for facilitating further stratification of more aggressive patients who would benefit from adjuvant therapy.

Highlights

Prostate cancer (PCa) remains the most common cancer and a leading cause of cancer-related death in men, with the most new patients diagnosed with the disease last year [1]
Using the gene set enrichment analysis (GSEA), we identified biological processes associated with the eight-long non-coding RNA (lncRNA) signature on the basis of the risk score (FDR < 0.01)
We found that six of the seven risky lncRNAs were highly expressed in prostate cancer across twelve different cancers (Student’s t-test, False discovery rate (FDR) < 0.05, Figure 6B), suggesting a cancerspecific pattern of the lncRNA signature

Summary

Introduction

Prostate cancer (PCa) remains the most common cancer and a leading cause of cancer-related death in men, with the most new patients diagnosed with the disease last year [1]. Despite the majority of prostate cancer patients are diagnosed at a potentially curable stage and treated with radical prostatectomy or other first-line treatments, a subset of patients will experience a recurrence, typically detected by a rise in serum prostate-specific antigen (PSA) levels [2, 3]. The ability to predict the risk of BCR soon after surgery could allow for initiation of secondary therapy as necessary to improve long term treatment outcomes [4, 5]. The prediction of the likelihood of BCR is critical for surveillance strategy of PCa patients and the molecular underpinnings of aggressive and indolent cancers may be essential to improve patient management and prognosis [8]

Methods

Results

Conclusion